The aging skeleton, particularly in post-menopausal women, loses bone mass after the age of 30-40. In persons over age 60-70, bone loss causes substantial disability principally owing to fractures of the vertebral column, femoral neck, and distal radius. Osteoporosis, a pathologic condition with bone loss over that anticipated for age, reflects an imbalance of bone formation versus bone resorption. The cause for this bone loss is largely unknown, although hormonal, metabolic, and mechanical (i.e. activity level) factors undoubtedly contribute to the loss. Consequently, therapy has often been directed toward hormonal replacement (e.g., estrogen), nutrition (e.g., Vit D, calcium, fluorides), and/or exercise (e.g., aerobics). The efficacy of the former is best established, while the latter two ar less well accepted. Recent evidence suggests the aging skeleton exhibits diminished response to mechanical factors: First, bones of old turkeys fail to respond to experimental mechanical regimens which increase bone formation in young adult birds. Second, primary human bone cells from osteoporotic patients respond less vigorously to strain than do bone cells from younger patients. based upon these preliminary observations, we hypothesize bone cells from osteoporotic patients respond less well to strain than do cells from non- osteoporotic patients. We will establish primary cell cultures from osteoporotic patients and determine whether their ability to proliferate or express matrix proteins in response to strain is reduced compared to cultures from age-matched non-osteoporotic controls. Established measures of proliferation (tritiated-thymidine uptake) and matrix expression (collagen synthesis, alkaline phosphatase, osteopontin, bone sialoprotein, osteonectin, osteocalcin) will be used. Cells will be grown on deformable substrates and strained at a magnitude, frequency, and duration physiologic for bone as a tissue. If we can confirm bone cells from osteoporotic patients respond less well to normal (or increased yet physiologically achievable) mechanical stimuli, and if the mechanism(s) can be identified, pharmacologic (or even genetic) approaches may restore strain sensitivity and afford more effective reduction of bone loss and treatment of osteoporosis.